Research Roundup: Clinical trial data, Mayaro virus, antimicrobial resistance, and more

For only the fourth time, the United Nations General Assembly (UNGA) convened a high-level meeting focused on health, which was held during the recent 71st UNGA. Following on the footsteps of the recently released “Review on Antimicrobial Resistance” report (commonly referred to as the O’Neill report), member states gathered to discuss antimicrobial resistance (AMR) and global and national commitments to address this threat. The report estimates that by 2050, 10 million people will die every year because of AMR and the rise of “superbugs.”  At the heart of the high-level meeting was an acknowledgement that the threat of AMR is very real, with multidrug-resistant tuberculosis accounting for one-third of AMR deaths every year and some infections, such as gonorrhea, now only treatable using the last class of antibiotics available. Member states want to address today the overuse of antibiotics, both in human and animal health, improvements in infection prevention and control, and supporting R&D that brings new medicines to market, in order to prevent a return to the days when a scraped knee could kill a child. Before diving into the outcomes of the high-level meeting, it is worth noting a few things that characterized the conversation. First, it is clear that there was a conscious effort on the part of the meeting organizers to use the platform of the General Assembly to reframe AMR as a “One Health” issue where agriculture, animal health, and human health are all aspects to be addressed in an AMR response. And while the World Health Organization (WHO) does not have the authority to direct policy for the Food and Agriculture Organization (FAO) or the World Organization for Animal Health (OIE), the General Assembly does, and it was clear (both from the framing of the summit and the text of the political declaration) that expectations are that the three United Nations (UN) agencies will work together for a coordinated response. Second, the sense of unanimous agreement in the room is something rarely seen at the UN. While there may have been some discussions around the edges of specific technical language, the impression was that member states and UN agencies are on the same page and committed to addressing AMR (unlike HIV and AIDS, for example, where even countries who endorsed the declaration had concerns around some of the action points). The political declaration on AMR, universally endorsed and formally adopted by member states, specifically calls for: Countries to commit to: Developing appropriate action plans and policies to address AMR. Mobilizing additional resources, including for innovative approaches and R&D. Ensuring that surveillance is part of these plans. Undertaking public awareness and education activities on AMR and the dynamics that drive it (including a focus on patient-driven demand for antibiotics). Utilizing a multisectoral model incorporating innovative partnerships and incentive mechanisms to pursue the “One Health” approach. WHO, FAO, and OIE should finalize a global development and stewardship framework to both protect the effectiveness of current technologies as well as to support the development of new technologies. WHO, FAO, OIE, the UN, multilateral development banks, and all other stakeholders should support the national, regional, and global action plans described above. The Secretary-General should establish a cross-UN coordinating group cochaired by WHO and the Secretary-General’s office to guide efforts on AMR, as well as to prepare a report for the 73rd General Assembly outlining progress and recommendations to accelerate it. In the context of the recent release of the report of the High-Level Panel on Access to Medicines (HLP), it is also worth noting that concerns around access to medicines are also evident in the AMR declaration. Unlike the broader access to medicines debate, however, there is a clear acknowledgment of the need to discourage overuse of antibiotics to preserve their effectiveness while ensuring that those who need them have access. Overall, the future implications of the high-level meeting and declaration will depend on what happens next. AMR is squarely on the international agenda and the meeting brought the global community together in an expression of shared desire to fix the problem, which is entirely positive. Unfortunately, shared desire is by no means sufficient to address a problem as complex as AMR. As one panelist said, “If I have three key points, they are implementation, implementation, implementation!” The determinant of the meeting’s success lies in whether the action plans are developed and then acted upon. As for the role of civil society and nongovernmental organizations, holding governments accountable over this is precisely where the global health community can step up through advocacy and mobilizing public pressure to create political will. 

Scientists have devised a Trojan horse strategy to prevent the Ebola virus from infecting human cells. To infect humans, the virus binds to the surface of a human cell, enters the cell, and then binds to the protein Niemann-Pick C1 (NPC1). Once it binds to NPC1, the virus can start replicating and spreading throughout the body. Consequently, the researchers first engineered two antibodies: one that targets the human protein NPC1 and another that targets the viral protein that binds to NPC1. However, they needed a Trojan horse: a molecule that could deliver the antibodies to the scene of the crime, deep inside human cells, where the virus binds to NPC1. The solution? The team synthesized each antibody with a third antibody that binds to the surface of the Ebola virus. In short, the team created two molecules by combining the antibody that could latch onto the virus with two antibodies that could prevent the virus from infecting human cells. Both combinations proved effective in the lab against all five strains of the Ebola virus and in mouse trials, one of the molecules effectively treated infected mice. Next, the molecules will be tested in nonhuman primates. A recent piece in STAT takes an in-depth look at the critical advances in hepatitis C research that paved the way for the development of Sovaldi, the first drug proven to cure hepatitis C. Hepatitis C was first discovered in 1989, however, the virus is notoriously difficult to reproduce in the lab. Consequently, the time and cost of producing the virus hindered research. Ralf Bartenschlager and Charles Rice, researchers at the University of Heidelberg and Rockefeller University, respectively, determined that certain mutations of the virus enabled select strains of the virus to survive in the lab, and engineered versions of the virus—deemed “replicons”—with those mutations. Using these replicons, drug companies were able to rapidly screen the efficacy of different compounds in combatting hepatitis C. Among these companies, the small biotech firm Pharmasset developed a particularly promising drug, which was eventually—after the company was acquired by Gilead Sciences—approved and marketed as Sovaldi. The drug became the first cure for Hepatitis C, however, its price tag of up to US$94,000 for the full regimen has impeded access to it. While existing evidence suggests that Zika infection has the greatest impact on fetal brain development during the first trimester of pregnancy, new research indicates that infection later in pregnancy can still have a devastating impact. Scientists at the University of Washington infected a pregnant monkey with the virus at the beginning of her third trimester, and in less than a month, significant damage to the fetus was reported: both the white matter in the brain and the head itself stopped growing. However, the team administered the virus in higher doses than would be found in individual mosquitoes, and researchers at the University of Wisconsin-Madison, who used lower doses, found no fetal brain damage after infecting four pregnant monkeys.